19-5851790-A-G

Variant names:

• chr19-5851790-A-G
• rs2306969
• ENST00000589276.1:n.303-714A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382748.2(FUT3):​c.-205-5172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,078 control chromosomes in the GnomAD database, including 44,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (44871 hom., cov: 31)
• Consequence: FUT3 NM_001382748.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 13 publications found

Genes affected

ENSG00000267709 (HGNC:):

FUT3 (HGNC:4014): (fucosyltransferase 3 (Lewis blood group)) The Lewis histo-blood group system comprises a set of fucosylated glycosphingolipids that are synthesized by exocrine epithelial cells and circulate in body fluids. The glycosphingolipids function in embryogenesis, tissue differentiation, tumor metastasis, inflammation, and bacterial adhesion. They are secondarily absorbed to red blood cells giving rise to their Lewis phenotype. This gene is a member of the fucosyltransferase family, which catalyzes the addition of fucose to precursor polysaccharides in the last step of Lewis antigen biosynthesis. It encodes an enzyme with alpha(1,3)-fucosyltransferase and alpha(1,4)-fucosyltransferase activities. Mutations in this gene are responsible for the majority of Lewis antigen-negative phenotypes. Differences in the expression of this gene are associated with host susceptibility to viral infection. [provided by RefSeq, Aug 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382748.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT3	NM_001382748.2		c.-205-5172T>C		intron	N/A	NP_001369677.1
	FUT3	NM_001382749.2		c.-140-5237T>C		intron	N/A	NP_001369678.1
	FUT3	NM_001382750.2		c.-151-5226T>C		intron	N/A	NP_001369679.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000267709	ENST00000589276.1	TSL:1	n.303-714A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116421 AN: 151960 Hom.: 44825 Cov.: 31

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.726

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.766 AC: 116532 AN: 152078 Hom.: 44871 Cov.: 31 AF XY: 0.768 AC XY: 57067 AN XY: 74340

African (AFR) AF: 0.747 AC: 30982 AN: 41450

American (AMR) AF: 0.802 AC: 12264 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2366 AN: 3470

East Asian (EAS) AF: 0.955 AC: 4923 AN: 5156

South Asian (SAS) AF: 0.760 AC: 3662 AN: 4820

European-Finnish (FIN) AF: 0.780 AC: 8260 AN: 10590

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51549 AN: 67982

Other (OTH) AF: 0.725 AC: 1535 AN: 2116

Alfa AF: 0.759 Hom.: 134339

Bravo AF: 0.770

Asia WGS AF: 0.826 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.40
PhyloP100		0.20
PromoterAI		0.016	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2306969; hg19: chr19-5851801;